Laboratório de Esquistossomose e Imunohelmintologia, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Curso de Enfermagem, Instituto de Ciências Biológicas e Saúde, Universidade Federal de Mato Grosso, Barra do Garça 78698-000, MG, Brazil.
Int J Mol Sci. 2023 Jun 16;24(12):10237. doi: 10.3390/ijms241210237.
eggs retained in host tissues induce innate cytokine release, contributing to the induction of Type-2 immune responses and granuloma formation, important to restrain cytotoxic antigens, but leading to fibrosis. Interleukin(IL)-33 participates in experimental models of inflammation and chemically induced fibrosis, but its role in -induced fibrosis is still unknown. To explore the role of the IL-33/suppressor of the tumorigenicity 2 (ST2) pathway, serum and liver cytokine levels, liver histopathology, and collagen deposition were comparatively evaluated in -infected wild-type (WT) and IL-33-receptor knockout (ST2) BALB/c mice. Our data show similar egg counts and hydroxyproline in the livers of infected WT and ST2 mice; however, the extracellular matrix in ST2 granulomas was loose and disorganised. Pro-fibrotic cytokines, such as IL-13 and IL-17, and the tissue-repairing IL-22 were significantly lower in ST2 mice, especially in chronic schistosomiasis. ST2 mice also showed decreased α-smooth muscle actin (α-SMA) expression in granuloma cells, in addition to reduced and mRNA levels and reticular fibres. Therefore, IL-33/ST2 signalling is essential for tissue repairing and myofibroblast activation during infection. Its disruption results in inappropriate granuloma organisation, partly due to the reduced type III and VI collagen and reticular fibre formation.
在宿主组织中滞留的虫卵会诱导先天细胞因子释放，有助于诱导 2 型免疫反应和肉芽肿形成，这对于抑制细胞毒性抗原很重要，但会导致纤维化。白细胞介素（IL）-33 参与炎症和化学诱导性纤维化的实验模型，但它在 感染诱导的纤维化中的作用尚不清楚。为了探讨 IL-33/肿瘤抑制因子 2（ST2）途径的作用，比较了感染野生型（WT）和 IL-33 受体敲除（ST2）BALB/c 小鼠的血清和肝组织细胞因子水平、肝组织病理学和胶原沉积。我们的数据显示，感染 WT 和 ST2 小鼠的卵计数和肝羟脯氨酸相似；然而，ST2 肉芽肿中的细胞外基质松散且无序。促纤维化细胞因子，如 IL-13 和 IL-17，以及组织修复的 IL-22，在 ST2 小鼠中明显降低，尤其是在慢性血吸虫病中。ST2 小鼠的肉芽肿细胞中 α-平滑肌肌动蛋白（α-SMA）表达也减少，此外， 和 mRNA 水平以及网状纤维减少。因此，IL-33/ST2 信号在 感染期间对组织修复和肌成纤维细胞激活至关重要。其破坏导致肉芽肿组织不当，部分原因是 III 型和 VI 型胶原以及网状纤维形成减少。
